Choroid plexus mast cells drive tumor-associated hydrocephalus. (https://pubmed.ncbi.nlm.nih.gov/38056463/)

These scientists wanted to understand why some people with brain tumors develop a condition called tumor-associated hydrocephalus (TAH), which can be very dangerous. They knew that something was happening in the brain, but they didn't know exactly what was causing it.

So, they decided to do a special kind of study called single-nucleus RNA sequencing and spatial transcriptomics. This is a way for scientists to look at the different parts of the brain and see what genes are being used by different cells.

What they found was really interesting! They discovered that there is a special group of cells called mast cells that are located in a part of the brain called the choroid plexus. These mast cells increase a lot when someone has TAH.

To figure out how these mast cells are causing problems, the scientists did some more experiments. They used a special technique called genetic fate tracing to track the mast cells and see what they were doing. They also made some mast cells in the brain not able to make a protein called tryptase.

What they discovered is that the mast cells with tryptase are causing damage to the cilia of the choroid plexus. Cilia are like tiny hairs that help move fluid in the brain. When the mast cells damage the cilia, it makes too much fluid in the brain, which leads to TAH.

The scientists also found mast cells in the choroid plexus of humans with TAH. They noticed that the levels of tryptase in the fluid around the brain were related to how bad the TAH was in people.

To see if they could help people with TAH, the scientists tested a medicine called BMS-262084. This medicine can stop the tryptase from causing damage in the brain. They found that this medicine could get into the brain and actually stop TAH from happening in animals. They also tested it on a model of the human brain and saw that it could protect the cilia from mast cell damage.

So, these scientists did a study to understand how mast cells are causing problems in the brain of people with brain tumors. They found that a protein called tryptase is causing damage to the cilia, which leads to TAH. They also found a medicine that can stop this damage and help people with TAH. This study is really important because it can help doctors find new ways to treat TAH and make people with brain tumors safer.

Li Y., Di C., Song S., Zhang Y., Lu Y., Liao J., Lei B., Zhong J., Guo K., Zhang N., Su S. Choroid plexus mast cells drive tumor-associated hydrocephalus. Cell. 2023 Dec 21;186(26):5719-5738.e28. doi: 10.1016/j.cell.2023.11.001. Epub 2023 Dec 5.